The overall object of this project is to test the hypothesis that activation of certain urinary bladder chemical carcinogens is mediated by prostaglandin endoperoxide synthetase, the hydroperoxidase activity of the prostaglandin endoperoxide synthetase enzyme being responsible for metabolism. It is proposed that this metabolic process proceeds in the renal inner medulla and the urinary bladder. Experiments have been specifically designed to test those hypotheses. The urinary bladder chemical carcinogens N-(4-(5-nitro-2-furyl)-2-thiazolyl) formamide (FANFT) and 2-amino-4-(5-nitro-2-furyl)-thiazole (ANFT) are being used in these studies. We feel that (1) we have clearly demonstrated the mechanism of both FANFT and ANFT metabolism by the hydroperoxidase activity of PES; (2) we have identified the reduced products of FANFT and 2-methyl-4-(5-nitro-2-furyl) thiazole to be nitriles by mass spectral analysis and have evidence for an N-hydroxyl intermediate during FANFT reduction, and (3) a preliminary rat feeding study has been completed demonstrating that aspirin can prevent the early morphological changes in bladder induced by FANFT.